Ovarian Cancer represents the most fatal type of gynecological malignancies. A number of processes are involved in the pathogenesis of ovarian cancer, especially within the tumor microenvironment. Angiogenesis represents a hallmark phenomenon in cancer, and it is responsible for tumor spread and metastasis in ovarian cancer, among other tumor types, as it leads to new blood vessel formation. In recent years angiogenesis has been given considerable attention in order to identify targets for developing effective anti-tumor therapies. Growth factors have been identified to play key roles in driving angiogenesis and, thus, the formation of new blood vessels that assist in “feeding” cancer. Such molecules include the vascular endothelial growth factor (VEGF), the platelet derived growth factor (PDGF), the fibroblast growth factor (FGF), and the angiopoietin/Tie2 receptor complex. These proteins are key players in complex molecular pathways within the tumor cell and they have been in the spotlight of the development of anti-angiogenic molecules that may act as stand-alone therapeutics, or in concert with standard treatment regimes such as chemotherapy. The pathways involved in angiogenesis and molecules that have been developed in order to combat angiogenesis are described in this paper.

We previously showed that ERCC1 19007 C>T polymorphism was associated with cancer-specific survival (CSS) after platinum-based chemotherapy in patients with advanced urothelial cancer (aUC). We aimed to confirm this association in a different cohort of patients. Genotyping of the 19007C>T polymorphism was carried out by polymerase chain reaction (PCR) amplification and restriction fragment length polymorphism (RFLP) in 98 aUC patients, treated with platinum-based chemotherapy. Median age of the patients was 68.8, 13.3% of them were female, 90.8% had ECOG PS of 0 or 1, and 48% received cisplatin-based chemotherapy. In addition to chemotherapy, 32.7% of the patients received immunotherapy, and 19.4% vinflunine. Eighty-one patients (82.7%) were carriers of the 19007T polymorphic allele: 46 (46.9%) were heterozygotes, and 35 (35.7%) were homozygotes. The ERCC1 polymorphism was not associated with CSS, progression-free (PFS), or overall (OS) survival in the total population. Nevertheless, there was a significant interaction between the prognostic significance of ERCC1 polymorphism and the use of modern immunotherapy: the T allele was associated with worse outcome in patients who received chemotherapy only, while this association was lost in patients who received both chemotherapy and immune checkpoint inhibitors. Our study suggests that novel therapies may influence the significance of ERCC1 polymorphism in patients with aUC. Its determination may be useful in the changing treatment landscape of the disease.

Ovarian cancer is one of the leading causes of cancer-related death among women. Disease relapse occurs in a high number of cases and treatment currently involves the use of chemotherapy with the use of paclitaxel and platinum-based agents. Resistance to the disease occurs in more than 70% of the cases. The immune system is increasingly becoming a target for intense research in order to study the host’s immune response against ovarian cancer. T cell populations, including NK T cells and Tregs, have been associated with disease outcome indicating their increasing clinical significance, having been associated with positive prognosis and as markers of disease progress, respectively. Cytokines may also be associated with positive prognosis and they can have a direct or indirect effect in mobilizing relevant T cells, thus eliciting an immune response. Harnessing the immune system capacity in order to induce anti-tumor response is a major challenge. This is achieved via the use of antibodies that can elicit an immune response or via the use of direct administration of cytotoxic T cell populations (e.g., CD8?). This review examines the recent developments in our understanding of the mechanisms of development of the immune response in ovarian cancer as well as its prognostic significance and the existing experience in clinical studies using factors associated with immune response, such as monoclonal antibodies, cytokines, vaccines and activated or expanded relevant autologous populations from peripheral blood.

GD3 mediated immune response via vascular endothelial growth factor in ovarian cancer